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Genomes and Genes | David GailaniSummaryAffiliation: Vanderbilt University Country: USA Publications
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Publications
The intrinsic pathway of coagulation: a target for treating thromboembolic disease?D Gailani
Department of Pathology, Vanderbilt University, Nashville, TN, USA
J Thromb Haemost 5:1106-12. 2007....- Intrinsic pathway of coagulation and arterial thrombosisDavid Gailani
Hematology Oncology Division, Vanderbilt University, 777 Preston Research Building, 2220 Pierce Ave, Nashville, TN 37232 6307, USA
Arterioscler Thromb Vasc Biol 27:2507-13. 2007..If factor XII or factor XI make similar contributions to thrombosis in humans, these proteases could be ideal targets for drugs to treat or prevent thromboembolic disease with minimal risk of therapy-associated bleeding... - Do platelets synthesize factor XI?D Gailani
Departments of Pathology and Medicine, Vanderbilt University, Nashville, Tennessee 37232 6307, USA
J Thromb Haemost 2:1709-12. 2004 - A cross-reactive material positive variant of coagulation factor XI (FXIP520L) with a catalytic defectD Gailani
Departments of Pathology and Medicine, Vanderbilt University, Nashville, TN 37232 6307, USA
J Thromb Haemost 5:781-7. 2007..Leucine can be incorporated at position 161 in FXIa, but would not form the extensive stabilizing network of hydrophobic interactions formed by Pro161... 
Structural and functional features of factor XID Gailani
Department of Pathology, Division of Hematology Oncology, Vanderbilt University, Nashville, TN 37232 6307, USA
J Thromb Haemost 7:75-8. 2009..1/2-FXIa activates FIX in a similar manner to FXIa. While the importance of the homodimeric structure of FXI is not certain, it may represent a strategy for binding to FIX and a platelet surface simultaneously...- Characterization of Novel Forms of Coagulation Factor XIa: independence of factor XIa subunits in factor IX activationStephen B Smith
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232, USA
J Biol Chem 283:6696-705. 2008..The results indicate that two forms of activated factor XI are generated during coagulation, and that each half of a factor XIa dimer behaves as an independent enzyme with respect to factor IX... - A role for factor XIIa-mediated factor XI activation in thrombus formation in vivoQiufang Cheng
Department of Pathology, Vanderbilt University, Nashville, TN 37232 6305, USA
Blood 116:3981-9. 2010..Since fXII deficiency does not impair hemostasis, targeted inhibition of fXI activation by fXIIa may be a useful antithrombotic strategy associated with a low risk of bleeding complications... - Activation of factor XI by products of prothrombin activationAnton Matafonov
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232 6305, USA
Blood 118:437-45. 2011.... - A classification system for cross-reactive material-negative factor XI deficiencyDmitri V Kravtsov
Department of Pathology, Vanderbilt University, Nashville, TN 37232-6307, USA
Blood 105:4671-3. 2005..The latter category likely accounts for many cases of dominant disease transmission... - Sucrose octasulfate selectively accelerates thrombin inactivation by heparin cofactor IISuryakala Sarilla
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
J Biol Chem 285:8278-89. 2010..The ex vivo HCII-dependent process may utilize the proposed model and suggests a potential for oversulfated disaccharides in controlling HCII-regulated thrombin generation... - Factor XI contributes to thrombin generation in the absence of factor XIIDmitri V Kravtsov
Department of Pathology, Vanderbilt University, Nashville, TN 37232 6307, USA
Blood 114:452-8. 2009..The results support a model in which fXI is activated by thrombin or another protease generated early in coagulation, with the resulting fXIa contributing to sustained thrombin generation through activation of factor IX... - Exosite-mediated substrate recognition of factor IX by factor XIa. The factor XIa heavy chain is required for initial recognition of factor IXTaketoshi Ogawa
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37069, USA
J Biol Chem 280:23523-30. 2005.... - A comparison of murine and human factor XID Gailani
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232 6350, USA
Blood 90:1055-64. 1997..The studies show that murine and human factor XI have similar structural and enzymatic properties. However, there may be variations in tissue specific expression and subtle differences in enzyme activity across species... - Defective binding of factor XI-N248 to activated human plateletsM F Sun
Department of Pathology and Medicine, Vanderbilt University, Nashville, TN, USA
Blood 98:125-9. 2001..Importantly, the defect in platelet binding would not be detected by routine clinical evaluation with an aPTT assay... 
Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasisChristoph Kleinschnitz
Department of Neurology, Institute for Clinical Biochemistry and Pathobiochemistry, University of Wurzburg, 97080 Wurzburg, Germany
J Exp Med 203:513-8. 2006..As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases...- Update on the physiology and pathology of factor IX activation by factor XIaStephen B Smith
Department of Pathology, Vanderbilt University, 777 Preston Research Building, 2220 Pierce Ave, Nashville, TN 37232 6307, USA
Expert Rev Hematol 1:87-98. 2008..Results from animal models and human population studies indicate that factor XI contributes to thromboembolic disease. This protease may therefore be a legitimate therapeutic target... - Dominant factor XI deficiency caused by mutations in the factor XI catalytic domainDmitri V Kravtsov
Department of Pathology, Vanderbilt University, Nashville, TN 37232, USA
Blood 104:128-34. 2004.... - Factor XI apple domains and protein dimerizationQ Cheng
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232 6307, USA
J Thromb Haemost 1:2340-7. 2003..The data indicate that FXI A2 and A3 make contributions to dimer formation. As these domains are involved in activities that require dimeric protein, it seems reasonable that they stabilize this conformation... - Identification of a binding site for glycoprotein Ibalpha in the Apple 3 domain of factor XIFrank A Baglia
Sol Sherry Thrombosis Research Center, Temple University School oof Medicine, Philadelphia, PA 19140, USA
J Biol Chem 279:45470-6. 2004..This interaction is important for the initiation of the consolidation phase of blood coagulation and the generation of thrombin at sites of platelet thrombus formation... - Role of Factor XII in hemostasis and thrombosis: clinical implicationsThomas Renne
Institute for Clinical Biochemistry and Pathobiochemistry Division, Julius Maximilians University Würzburg, Josef Schneider Strasse 2 Building, D 97080 Wurzburg, Germany
Expert Rev Cardiovasc Ther 5:733-41. 2007.... - The factor IX gamma-carboxyglutamic acid (Gla) domain is involved in interactions between factor IX and factor XIaAysar Aktimur
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232, USA
J Biol Chem 278:7981-7. 2003..The data demonstrate that factor XIa binds with comparable affinity to factors IX and IXabeta and that the interactions are dependent on the factor IX Gla domain... - Factor V Leiden protects against blood loss and transfusion after cardiac surgeryBrian S Donahue
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tenn 37232, USA
Circulation 107:1003-8. 2003.... - Disposition of tissue factor pathway inhibitor during cardiopulmonary bypassB S Donahue
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
J Thromb Haemost 4:1011-6. 2006..We have investigated the structural and functional properties of plasma TFPI during CPB to further characterize how TFPI is altered during this procedure... - Gene targeting in hemostasis. factor XID Gailani
Departments of Pathology and Medicine, Vanderbilt University, Nashville, TN, USA
Front Biosci 6:D201-7. 2001..Severe FXI deficiency partially ameliorates the devastating hypercoagulable state associated with severe protein C deficiency, indicating that FXI plays a role in certain thrombotic conditions... - Model for a factor IX activation complex on blood platelets: dimeric conformation of factor XIa is essentialD Gailani
Department of Pathology, Vanderbilt University, Nashville, TN, USA
Blood 97:3117-22. 2001.... - A murine model of factor XI deficiencyD Gailani
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232 6305, USA
Blood Coagul Fibrinolysis 8:134-44. 1997..The factor XI deficient mice are a unique tool for evaluating the role of factor XI in normal hemostasis and pathologic coagulation... - Identification of mutations and polymorphisms in the factor XI genes of an African American family by dideoxyfingerprintingD Martincic
Department of Pediatrics, Pathology, and Medicine, Vanderbilt University, Nashville, TN, USA
Blood 92:3309-17. 1998..4%, 19%, and 18%, respectively. This suggests that there is considerable genetic heterogeneity in the factor XI gene... - Anticoagulant-induced skin necrosis in a patient with hereditary deficiency of protein SD Gailani
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232 6305, USA
Am J Hematol 60:231-6. 1999..Because many patients who develop warfarin-induced skin necrosis have been treated initially with heparin, it would seem prudent to consider HIT in these situations... - Activation of factor IX by factor XIaD Gailani
Department of Pathology, Vanderbilt University, Nashville, TN 37232 6305, USA
Trends Cardiovasc Med 10:198-204. 2000..The data suggest, however, that this reaction differs significantly from other protease-substrate interactions on the platelet surface. This is likely to be due, in part, to the unusual structure of the factor XI molecule... - The intrinsic pathway of coagulation is essential for thrombus stability in miceThomas Renne
Institute for Clinical Biochemistry and Pathobiochemistry, Julius Maximilians University Würzburg, Josef Schneider Strasse 2, D 97080 Wurzburg, Germany
Blood Cells Mol Dis 36:148-51. 2006..These findings demonstrate that FXII-mediated fibrin formation is crucial for pathological arterial thrombosis but not for hemostasis and suggest that FXII could be an ideal target for safe anticoagulation... - A Sequential Mechanism for Exosite-mediated Factor IX Activation by Factor XIaYipeng Geng
From the Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee 37232 and
J Biol Chem 287:38200-9. 2012..Initial binding of fIX and fIXα requires an exosite on the fXIa A3 domain, but not the A2 or catalytic domain... - The effects of intrinsic pathway protease deficiencies on plasminogen-deficient miceQiufang Cheng
Hematology Oncology Division, Department of Pathology, Vanderbilt University, 777 MRB II, 2220 Pierce Ave, Nashville, TN 37232 6307, USA
Blood 106:3055-7. 2005..Activated fXI is thought to function primarily as a fIX activator; however, our observation suggests that fXI may have functions in regulation of inflammation or tissue repair distinct from its role in coagulation... - Factor XI messenger RNA in human plateletsD Martincic
Departments of Pediatrics, Pathology, and Medicine, Vanderbilt University, Nashville, TN 37232 6305, USA
Blood 94:3397-404. 1999..The data do not support the premise that the 220 kD platelet protein that cross-reacts with FXI antibodies is a product of an alternatively spliced mRNA from the FXI gene... - Characterization of the H-kininogen-binding site on factor XI: a comparison of factor XI and plasma prekallikreinThomas Renne
Institute for Biochemistry II, Johann Wolfgang Goethe University of Frankfurt, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
J Biol Chem 277:4892-9. 2002..Our data show that HK binding to FXI involves multiple apple domains, with F2 being most important. The findings demonstrate a similarity in mechanism for FXI and prekallikrein binding to HK... - Survival advantage of coagulation factor XI-deficient mice during peritoneal sepsisErik I Tucker
Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon 97239, USA
J Infect Dis 198:271-4. 2008..This finding suggests that FXI contributes to coagulopathy and/or inflammation during sepsis and that pharmacologic inhibition of FXI activity may alter the course and outcome of some infections... - Structural role of Gly(193) in serine proteases: investigations of a G555E (GLY193 in chymotrypsin) mutant of blood coagulation factor XIAmy E Schmidt
UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
J Biol Chem 279:29485-92. 2004..Such arguments will apply to other serine proteases with substitutions of Gly(193) with a non-glycine residue... 
Acquired factor XI deficiency in a child with membranoproliferative glomerulonephritisMeghann Pine McManus
Division of Pediatric Hematology Oncology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
Pediatr Blood Cancer 59:173-5. 2012..Antibody-mediated clearance of prothrombin or factor X can cause acquired deficiencies of these proteins. This is the first report, to our knowledge, of an antibody that causes fXI deficiency by this mechanism...- Defective thrombus formation in mice lacking coagulation factor XIIThomas Renne
Institute of Clinical Biochemistry and Pathobiochemistry, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Wurzburg, 97078 Wurzburg, Germany
J Exp Med 202:271-81. 2005..The results establish FXII as essential for thrombus formation, and identify FXII as a novel target for antithrombotic therapy... - Factor XI/ADAMTS13 complexes are quantitatively insignificant in human plasmaPatricia J Anderson
Department of Medicine, Washington University School of Medicine, 660 S Euclid, Box 8066, St Louis, MO 63110, USA
Haematologica 92:1419-22. 2007..These results suggest that ADAMTS13/FXI complexes are insignificant in plasma and unlikely to affect the function of either protein during normal hemostasis or in TTP... - Tissue factor and platelet glycoprotein Ib-alpha alleles are associated with age at first coronary bypass operationBrian S Donahue
Department of Anesthesiology, Vanderbilt University, Nashville, Tennessee 37232, USA
Anesthesiology 99:1287-94. 2003..The authors tested this hypothesis in a cardiac surgery population... - Cloning and characterization of the human factor XI gene promoter: transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha ) is required for hepatocyte-specific expression of factor XITakashi Tarumi
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232 6307, USA
J Biol Chem 277:18510-6. 2002..When a rat HNF-4alpha expression construct is co-transfected into HeLa cells, factor XI promoter activity is enhanced approximately 10-fold. We conclude that HNF-4alpha is required for hepatocyte-specific expression of factor XI... - Contributions of basic amino acids in the autolysis loop of factor XIa to serpin specificityAlireza R Rezaie
Edward A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri 63104, USA
Biochemistry 45:9427-33. 2006..Arg-147 was also required for inhibition by alpha(1)-PI. Cumulatively, the results demonstrate that basic amino acids in the autolysis loop of fXIa are important determinants of serpin specificity... - Factor XI protein in human pancreas and kidneyQiufang Cheng
Thromb Haemost 100:158-60. 2008 - Molecular cloning and biochemical characterization of rabbit factor XIDipali Sinha
The Sol Sherry Thrombosis Research Center, Department of Biochemistry, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, U S A
Biochem J 367:49-56. 2002.... - Functional role of residue 193 (chymotrypsin numbering) in serine proteases: influence of side chain length and beta-branching on the catalytic activity of blood coagulation factor XIaAmy E Schmidt
UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery and Molecular Biology Institute, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
Biochemistry 47:1326-35. 2008..In conclusion, enzyme activity is impaired in FXIa when Gly193 is replaced by a non-Gly residue, and residues with side chains that branch at the beta-carbon have the greatest effect on catalysis and binding of substrates... - Fine mapping of the H-kininogen binding site in plasma prekallikrein apple domain 2Thomas Renne
Institute of Clinical Biochemistry and Pathobiochemistry, Julius Maximilians University at Würzburg, Josef Schneider Strasse 2, D 97080 Wurzburg, Germany
Int Immunopharmacol 2:1867-73. 2002..This sequence is conserved in the A2 domain of the related protease factor XI, explaining the unusual strong cross-reactivity of PHK6 with factor XI, as well as the similar HK-binding characteristics of PPK and factor XI...
Research Grants
- Factor Xl in Vascular ThrombosisDavid Gailani; Fiscal Year: 2010..We are looking for new targets in blood for anticoagulation therapy that will not be associated with high bleeding risk. ..
- Physiology and Molecular Biology of Factor XIDavid Gailani; Fiscal Year: 2009..This protease, therefore, is a legitimate target for novel anti- thrombotic therapies that should carry a lower risk of life-threatening bleeding, when compared to currently available anticoagulants. ..
- Physiology and Molecular Biology of Factor XIDavid Gailani; Fiscal Year: 2007..abstract_text> ..
- Factor Xl in Vascular ThrombosisDavid Gailani; Fiscal Year: 2007..We are looking for new targets in blood for anticoagulation therapy that will not be associated with high bleeding risk. ..
- FACTOR XI PHYSIOLOGY AND MOLECULAR BIOLOGYDavid Gailani; Fiscal Year: 2004....
- FACTOR XI PHYSIOLOGY AND MOLECULAR BIOLOGYDavid Gailani; Fiscal Year: 2000..The studies will substantially increase our knowledge of factor XI biochemistry and physiology and provide a firmer knowledge base from which to study the contribution of this protein to thromboembolic diseases. ..
- Physiology and Molecular Biology of Factor XIDavid Gailani; Fiscal Year: 2010..This protease, therefore, is a legitimate target for novel anti- thrombotic therapies that should carry a lower risk of life-threatening bleeding, when compared to currently available anticoagulants. ..